The effectiveness of radiotherapy would be improved if radiosensitizing drugs were used which acted differentially in sensitizing cancer cells more than normal tissues. Recent studies of lucanthone (Miracil D), 1-diethylamino-ethylamino-4-methyl-10-thioxanthenone, a relatively non-toxic drug widely used in the treatment of schistosomiasis, indicate that it radiosensitizes by inhibiting repair or radiation damage, localizes in certain neoplastic tissues more than in adjacent skin and muscle, and causes a substantial radiosensitization of mouse tumors with little or no sensitization of adjacent normal tissues. In addition, limited clinical results indicate that lucanthone halved the 50% regression time following radiotherapy for the two tumor types tested. The objectives of this project are to determine in mice (1) the optimum timing and optimum radiation dose rate for effective use of this repair-inhibiting drug in combination with radiation therapy, (2) the extent of tumor radiosensitization by lucanthone in various fractionation schemes which allow more opportunity for repair than single fraction treatments, (3) the possible role of metabolism of lucanthone in its radiosensitizing action, and (4) the extent of possible radiosensitization by lucanthone of several important dose-limiting normal tissues. The results will help to define more nearly optimum treatment parameters and favorable treatment situations for use of this promising radiosensitizing drug in radiation therapy.